A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine
| Autor: | Aileen Ebenig, Arne Auste, Samada Muraleedharan, Barbara S. Schnierle, Ralph S. Baric, Christoph Schürmann, Cindy Hörner, Tatjana Scholz, Kenneth H. Dinnon, Michael D. Mühlebach, Maike Herrmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
COVID-19 Vaccines T cell T-Lymphocytes Measles Vaccine Antibodies Viral measles vaccine platform Microbiology Virus effective immunity Measles virus 03 medical and health sciences Mice 0302 clinical medicine Pandemic medicine Animals Humans Gene Pandemics chemistry.chemical_classification Multidisciplinary biology Th1 immune bias SARS-CoV-2 COVID-19 Th1 Cells Biological Sciences biology.organism_classification Virology 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus biology.protein Antibody Glycoprotein CD8 |
| Zdroj: | Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2014468117 |
| Popis: | Significance The COVID-19 pandemic has already caused over 1 million deaths. Therefore, effective vaccine concepts are urgently needed. In search of such a concept, we have analyzed a measles virus-based vaccine candidate targeting SARS-CoV-2. Using this well-known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity, yielding antiviral efficacy in vivo with the desired immune bias. Consequently, no immunopathologies became evident during challenge experiments. Moreover, the candidate still induces immunity against the measles, recognized as a looming second menace, when countries are forced to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles-based COVID-19 vaccine could be the solution for two significant public health threats. The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines. |
| Databáze: | OpenAIRE |
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